The purpose of this study is to compare how long the participants are disease-free
(progression-free survival) and and the length of time until a participant dies (overall
survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin
calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus
either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat
sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf
murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or
metastatic colorectal cancer who have previously received chemotherapy.

A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy

Colorectal Neoplasms

Metastatic Colorectal Cancer

Colorectal cancer

Anal cancer

Colon cancer

Rectal cancer

Gastrointestinal Cancer

Advanced Solid Tumors

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Amivantamab

Irinotecan

Cetuximab

5-fluorouracil

Leucovorin calcium/Levoleucovorin

Bevacizumab

A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy

PFS is defined as the time from randomization until the date of objective disease
progression or death (due to any cause), whichever comes first, as assessed by BICR using
response evaluation criteria in solid tumors (RECIST) version (v)1.1. Participants who
have not progressed or have not died at the time of analysis will be censored at their
last evaluable RECIST v1.1 assessment date.

OS is defined as the time from the date of randomization to the date of participant's
death due to any cause.

ORR is defined as the percentage of randomized participants achieving partial response
(PR) or complete response (CR), as determined by BICR using RECIST v1.1 criteria.

PFS is defined as the time from randomization until the date of objective disease
progression or death (due to any cause), whichever comes first, as assessed by
investigator.

ORR is defined as the percentage of randomized participants achieving PR or CR, as
assessed by investigator.

DoR is defined as time from the date of first documented response (CR or PR) until the
date of documented progression or death, whichever comes first, for participants who have
PR or CR as assessed by BICR.

DoR is defined as time from the date of first documented response (CR or PR) until the
date of documented progression or death, whichever comes first, for participants who have
PR or CR as assessed by investigator.

PFS2 is defined as the time from randomization until the date of second objective disease
progression, after initiation of subsequent systemic anticancer therapy, based on
investigator assessment or death, whichever comes first.

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable
disease (with a minimum duration of 7 weeks) as defined by BICR using RECIST v1.1.

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable
disease (with a minimum duration of 7 weeks) as assessed by investigator.

Time to treatment failure is defined as time from randomization to discontinuation of
therapy for any reason including death, progression, toxicity, or initiation of new
anticancer therapy.

Curative resection (R0) rate is defined as the percentage of randomized participants who
underwent curative-intent surgery where the residual tumor classification was R0.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical
(investigational or non investigational) product. An AE does not necessarily have a
causal relationship with the treatment. Severity of AEs will be graded according to the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
v5.0. by using standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms;
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe
but not immediately life threatening; hospitalization or prolongation of hospitalization
indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE.

Participants with abnormalities in laboratory values (such as serum chemistry,
hematology) will be reported.

The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the
health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30
includes 5 functional scales, 3 symptom scales, a global health status / quality of life
scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response
scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are
rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher
scores indicate greater functioning, better global health status, and more severe
symptoms.

Time to worsening in symptoms and functioning as measured by EORTC QLQ-C30 score will be
reported. The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the
health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30
includes 5 functional scales, 3 symptom scales, a global health status / quality of life
scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response
scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are
rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher
scores indicate greater functioning, better global health status, and more severe
symptoms.

The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of
participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms
(gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image,
weight, and anxiety) that are associated with colorectal cancer and its treatments.
Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4
"Very much." All scores are linearly converted into a scale from 0 to 100. Higher scores
indicate greater functioning and more severe symptoms.

Time to worsening in symptoms and functioning as measured by EORTC QLQ-CR29 will be
reported. EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the
HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate
symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body
image, weight, and anxiety) that are associated with colorectal cancer and its
treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at
all" to 4 "Very much." All scores are linearly converted into a scale from 0 to 100.
Higher scores indicate greater functioning and more severe symptoms. Change from baseline
in the EORTC QLQ-CR29 score will be reported.

EORTC item 168 is a single item used to measure the overall impact of treatment side
effects. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at
all" to 4 "Very much. Higher scores indicates severe symptoms.

Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil,
leucovorin calcium [folinic acid] or levoleucovorin, and irinotecan) as a chemotherapy
regimen for 28-days treatment cycles and will continue to receive the treatment until
radiographic disease progression or other discontinuation criteria are met.

Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a
chemotherapy regimen for 28-days treatment cycles and will continue to receive the
treatment until radiographic disease progression or other discontinuation criteria are
met.

Ironwood Cancer and Research Center

Arizona Oncology Associates PC NAHOA

St. Bernard's Medical Center

CBCC Global Research

Los Angeles Cancer Network

Cancer and Blood Specialty Clinic

USC Norris Comprehensive Cancer Center

UCLA

Providence Medical Foundation

Torrance Memorial Physicians Network

University of Colorado Denver Anschultz Medical Campus

Rocky Mountain Cancer Centers

Eastern Connecticut Hematology & Oncology Assoc.

Florida Cancer Specialists South

Mount Sinai Medical Center Campus

AdventHealth Cancer Institute

Florida Cancer Specialists North Region

Florida Cancer Specialists East

University Cancer And Blood Center LLC

Grady Memorial Hospital

Piedmont Cancer Institute

Winship Cancer Institute Emory University

Mary Bird Perkins Cancer Center

MedStar Franklin Square Medical Center

University of Michigan Rogel Cancer Center

Cancer And Hematology Centers of Western Michigan PC

Hattiesburg Clinic

Washington University School Of Medicine

Nebraska Cancer Specialists

Astera Cancer Care

Perlmutter Cancer Center at NYU Long Island

NYU Langone Medical Center NYU Hematology Associates

New York Cancer and Blood Specialists

Montefiore Einstein Comprehensive Cancer Center

University Hospital of Cleveland

Alliance Cancer Specialists at Main Line

Fox Chase Cancer Center

University Of Pittsburgh Medical Center UPMC Hillman Cancer Center

Tennessee Oncology

SCRI Oncology Partners

Texas Oncology West Texas

Texas Oncology DFW

MD Anderson Cancer Center

Texas Oncology - San Antonio

Scott And White Memorial Hospital

UT Health East Texas HOPE Cancer Center

Virginia Cancer Specialists

VCU Massey Comprehensive Cancer Center

Providence Regional Cancer System

Concord Hospital

Warringal Private Hospital

Queen Elizabeth Hospital

Western Health Sunshine Hospital

Institut Jules Bordet

UZ Antwerpen

AZ Maria Middelares

Jolimont

Az Groeninge

Universitair Ziekenhuis Leuven

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Fundacao Pio XII

Fundacao Universidade de Caxias do Sul

Fundacao Doutor Amaral Carvalho

Hospital Nossa Senhora da Conceicao S A

Hospital Santa Izabel Santa Casa de Misericordia da Bahia

Fundacao Faculdade Regional De Medicina S Jose Rio Preto Hospital De Base

Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo

Fundacao Antonio Prudente A C Camargo Cancer Center

Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia

Peking University First Hospital

Beijing Friendship Hospital Capital Medical University

Beijing Cancer Hospital

The First Bethune Hospital of Jilin University

Hunan Cancer hospital

West China Hospital of Sichuan University

Ganzhou Cancer Hospital

Sun Yat Sen University Cancer Center

The Sixth Affiliated Hospital Sun Yat sen University

Guangdong Provincial People's Hospital

The Second Affiliated Hospital of Zhejiang University

Zhejiang Cancer Hospital

Harbin medical university cancer hospital

Huizhou Central People's Hospital

Gansu Provincial Cancer Hospital

The First Affiliated Hospital of NanChang University

Fudan University Shanghai Cancer Center

Liaoning Cancer Hospital and Institute

Tianjin Medical University Cancer Institute and Hospital

Hubei Cancer Hospital

Institut Sainte Catherine

Hopital Haut Leveque

CHU De Poitiers

Charite Universitatsmedizin Berlin Campus Virchow Klinikum

Krankenhaus NorthWest

National Center for Tumor Diseases NCT

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Klinikum der Universitaet Muenchen

Queen Mary Hospital

Prince Of Wales Hospital

Curative resection (R0) rate is defined as the percentage of randomized participants who
underwent curative surgery.

Banner MD Anderson Cancer Center

Asian Institute Of Gastroenterology

Deenanath Mangeshkar Hospital and Research Centre

Istituto Dei Tumori Di Milano

National Cancer Center Hospital East

Aichi Cancer Center

National Hospital Organization Osaka National Hospital

The University of Osaka Hospital

Hospital Pulau Pinang

University Malaya Medical Centre

COI Centro Oncologico Internacional Tijuana

Radboud University Medical Center

ETZ TweeSteden

Bialostockie Centrum Onkologii im Marii Sklodowskiej Curie w Bialymstoku

Wojewodzki Szpital Specjalistyczny

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy

Trials at a glance

Trials at a glance

A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy

Outcome measures

Primary outcome measures

Secondary outcome measures